Mitochondria are subcellular organelles present in cells of all tissues (except sperm) that carry out the oxidative-phosphorylation (OXPHOS) metabolic reactions that are essential for and central to cellular energy production. Abnormal mitochondrial function profoundly and adversely affects human health and performance, contributing to the development of numerous diseases including diabetes, ophthalmologic defects, deafness, neuromuscular disorders, defects in oxidative phosphorylation, and possibly cancer. Additionally, a decline in mitochondrial function is believed to be the major contributor to reduced physical and perhaps cognitive capacity during human aging. Unlike lower eukaryotes such as yeasts, cells in multicellular eukaryotes require fully-functioning mitochondria for viability. Mutations in these mitochondrial-associated genes (or damage to regulatory or structural mitochondrial proteins) can significantly impair mitochondrial function and result in a progressive reduction in energy output, significantly below that needed in body tissues. This can result in the manifestation of aging-related endpoints including reduction or loss of memory, hearing, vision, stamina, and the onset of age-related diseases including Parkinson's disease, neuromuscular defects, and cancer. Our research focus is the identification and characterization of genetic and biochemical factors associated with mitochondrial DNA (mtDNA) maintenance and the fidelity of the mtDNA polymerase.